Various publications, including patents, published applications, technical articles and scholarly articles are cited throughout the specification. Each of these cited publications is incorporated by reference herein, in its entirety. Full citations for publications not cited fully within the specification are set forth at the end of the specification.
Adipose tissue is a useful energy depot, important for example. for the survival of wild animals because their daily food supply may be limited or uncertain at times. However, the amount of adipose tissue (body fat) in wild animals is much lower than that of domesticated animals. As a result of accumulation of excess adipose tissue, due, for example, to overconsumption of calories and/or lack of exercise, mammals such as humans, or companion animals (e.g. dogs and cats) become overweight or obese.
Animals accumulate fat by eating more calories than are required for energy outputs. If the intake of energy (in the form of calories) exceeds energy expenditure, body fat accumulates. The basal metabolic rate (BMR) is a measure of the energy expended by an animal in a resting state; BMR represents the energy required to perform only normal body functions. If fat is to be removed from the body, fewer calories must be consumed, or more calories must be expended. Physical activity changes the expenditure of energy. Physical inactivity minimizes energy expenditure, yet may contribute to increased food intake. Thus, prolonged or marked decreases in physical activity may lead to obesity.
It has been estimated that in the United States and Europe, 25-44% of domesticated dogs and cats are overweight or obese. (Hand, M S et al. (1989); and, Scarlett, J M et al. (1994)). Animals, such as dogs, that are overweight or obese have health problems, especially in middle age (e.g. dogs that are between about 6-8 years old). If these weight-related health problems remain uncorrected, the risks increase for an animal to develop chronic diseases such as diabetes mellitus, cancer, hypertension, pulmonary, cardiovascular, or degenerative joint disease. In addition, an overweight dog may suffer from skin problems, reduced resistance to infectious diseases, and increased rate of mortality.
Excessive accumulation of body fat occurs when the synthesis of fat exceeds its breakdown. It is known that obesity places increased stress on an animal's body. Increased oxidative stress is believed to be at least partially responsible for the increased risk of the above-mentioned diseases associated with obesity. Substances that inhibit fat synthesis and/or promote fat breakdown may be useful to reduce or prevent excessive accumulation of fat, or obesity in animals, whereas antioxidants may be useful to minimize oxidative damage.
In addition to its role as a storage site for energy surplus, adipose tissue is an endocrine organ. The endocrine system controls a variety of functions in an animal's body through hormones and cytokines. The homeostasis of endocrine hormones, including sex hormones may be disturbed in obese individuals.
Among the sex hormones, estrogens and androgens are now known to play a very important role in energy metabolism, the metabolism and development of adipose tissue, and maintenance of normal body composition. Estrogen, in both male and female animals, plays an important role in regulating the function and development of adipocytes (Cooke, P S et al. (2004)). Thus, menopause in humans and the spaying/neutering of animals are risk factors for obesity development. Indeed, diminished levels of either estrogen or testosterone have been correlated with increased accumulation of body fat. (Pergola, G D (2000); Cookem P S et al. (2004); and, Mohamed, M K et al. (2000)).
The sex hormones may affect adipose tissue in different ways, for example, by affecting the number and size of adipocytes, lipogenesis, and lipolysis, modulating appetite or energy expenditure, and the like. (Pergola G D, 2000; Cooke P S et al., 2004; and, Naaz, A et al., 2003). In this regard, hormone replacement therapy and dietary supplementation have been studied as a means to reverse the effects. (Sayegh R et al., 1999; and, Bhathena S J et al., 2002).
Surgical procedures such as neutering, spaying, ovariectomy, castration, and the like, are frequently performed on animals for population control. However, weight gain is commonly observed in animals following these procedures. (Harper E J et al., 2001; and, Robertson I D, 2003). It is believed that the weight gain is a consequence of the loss of sex hormone production by the sex organs—following the removal of the sex organs there are markedly decreased levels of endogenous sex hormones.
With respect to dietary supplementation, mounting evidence suggests that phytoestrogens may play a role in enhancing lipid metabolism and diminishing deposition of adipose tissue. (Naaz A et al., 2003; Bhathena S J et al., 2002; and Wagner J D et al., 2003). Phytoestrogens are compounds that are produced by plants and have a structure similar to mammalian estrogens (Clarkson T B et al., 2001),. They are capable of interacting with estrogen receptors on adipose tissue in many animal species, including humans, rats, monkeys, and mice. (Naaz A et al., 2003; and, Linford N J et al., 2002). Phytoestrogens are subdivided into three major classifications, coumestans, lignans, and isoflavones. Isoflavones have demonstrated positive effects with respect to reducing adipose deposition, reducing serum low density lipoproteins (LDLs), inhibiting atherosclerosis, and the like, in subjects to which they were administered. (Bhathena S J et al., 2002; Naaz A et al., 2003; Wagner J D et al., 2003; Kawakami Y et al., 2004; and, Fang Y C et al., 2004).
There is thus a need in the art would be to provide compositions and methods that facilitate preserving lean body mass while preventing accumulation of body fat in subjects who are not on a diet regimen or who are consuming more than their minimum caloric requirements.